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Published in: Annals of Hematology 7/2020

01-07-2020 | Lymphoma | Original Article

The interval between progression and therapy initiation is the key prognostic parameter in relapsing diffuse large B cell lymphoma: analysis from the Czech Lymphoma Study Group database (NIHIL)

Authors: Andrea Janikova, Jozef Michalka, Zbynek Bortlicek, Renata Chloupkova, Vit Campr, Natasa Kopalova, Pavel Klener, Katerina Benesova, Jitka Hamouzova, David Belada, Vit Prochazka, Robert Pytlik, Jan Pirnos, Juraj Duras, Heidi Mocikova, Marek Trneny

Published in: Annals of Hematology | Issue 7/2020

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Abstract

Relapsing diffuse large B cell lymphomas (rDLBCL) represent a heterogeneous disease. This heterogeneity should be recognized and reflected, because it can deform the interpretation of clinical trial results. DLBCL patients with the first relapse and without CNS involvement were identified in the Czech Lymphoma Study Group (CLSG) database. Interval-to-therapy (ITT) was defined as the time between the first manifestation of rDLBCL and the start of any treatment. The overall survival (OS) of different ITT cohorts (< 7 vs. 7–21 vs. > 21 days) was compared. In total, 587 rDLBCLs (51.8% males) progressed with a median of 12.8 months (range 1.6 to 152.3) since the initial diagnosis (2000–2017). At the time of relapse, the median age was 67 years (range 22–95). First-line therapy was administered in 99.3% of the patients; CHOP and anti-CD20 were given to 69.2% and 84.7% of the patients, respectively. The salvage immune/chemotherapy was administered in 88.1% of the patients (39.2% platinum-based regimen). The median ITT was 20 days (range 1–851), but 23.2% of patients initiated therapy within 7 days. The 5-year OS was 17.4% (range 10–24.5%) vs. 20.5% (range 13.5–27.4%) vs. 42.2% (range 35.5–48.8%) for ITT < 7 vs. 7–21 vs. > 21 days (p < 0.001). ITT was associated with B symptoms (p 0.004), ECOG (p < 0.001), stage (p 0.002), bulky disease (p 0.005), elevated LDH (p < 0.001), and IPI (p < 0.001). The ITT mirrors the real clinical behavior of rDLBCL. There are patients (ITT < 7 days) with aggressive disease and a poor outcome. Conversely, there are rDLBCLs with ITT ≥ 21 days who survive for a long time.
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Literature
1.
go back to reference Al-Hamadani M, Habermann TM, Cerhan JR et al (2015) Non-Hodgkin lymphoma subtype distribution, geodeomographic patterns, and survival in the US: a longitudinal analysis of the national cancer data base from 1998 to 2011. Am J Hematol 90:790–795CrossRef Al-Hamadani M, Habermann TM, Cerhan JR et al (2015) Non-Hodgkin lymphoma subtype distribution, geodeomographic patterns, and survival in the US: a longitudinal analysis of the national cancer data base from 1998 to 2011. Am J Hematol 90:790–795CrossRef
2.
go back to reference Habermann TM, Weller EA, Morisson VA et al (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24:3121–3127CrossRef Habermann TM, Weller EA, Morisson VA et al (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24:3121–3127CrossRef
3.
go back to reference Pfreundschuh M, Trumpel L, Osterborg A et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large B-cell lymphoma: a randomised controlled trial by the MabThera International (MInT) group. Lancet Oncol 7:379–391CrossRef Pfreundschuh M, Trumpel L, Osterborg A et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large B-cell lymphoma: a randomised controlled trial by the MabThera International (MInT) group. Lancet Oncol 7:379–391CrossRef
4.
go back to reference Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O'Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM (2005) Introduction of combined CHOP plus rituximab dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 23:5027–5033CrossRef Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O'Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM (2005) Introduction of combined CHOP plus rituximab dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 23:5027–5033CrossRef
5.
go back to reference Howlander N, Mariotto AB, Besson C et al (2017) Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era. Cancer 123:3326–3334CrossRef Howlander N, Mariotto AB, Besson C et al (2017) Cancer-specific mortality, cure fraction, and noncancer causes of death among diffuse large B-cell lymphoma patients in the immunochemotherapy era. Cancer 123:3326–3334CrossRef
6.
go back to reference Coiffier B, Lepage E, Briére J et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. NEJM 346:235–242CrossRef Coiffier B, Lepage E, Briére J et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. NEJM 346:235–242CrossRef
7.
go back to reference Coiffier B, Thieblemont C, Den Van Neste E et al (2010) Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l'Adulte. Blood 116:2040–2045CrossRef Coiffier B, Thieblemont C, Den Van Neste E et al (2010) Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l'Adulte. Blood 116:2040–2045CrossRef
8.
go back to reference Farooq U, Maurer MJ, Thompson CA, Thanarajasingam G, Inwards DJ, Micallef I, Macon W, Syrbu S, Lin T, Lin Y, Ansell SM, Nowakowski GS, Habermann TM, Cerhan JR, Link BK (2017) Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy. Br J Haematol 179:50–60CrossRef Farooq U, Maurer MJ, Thompson CA, Thanarajasingam G, Inwards DJ, Micallef I, Macon W, Syrbu S, Lin T, Lin Y, Ansell SM, Nowakowski GS, Habermann TM, Cerhan JR, Link BK (2017) Clinical heterogeneity of diffuse large B cell lymphoma following failure of front-line immunochemotherapy. Br J Haematol 179:50–60CrossRef
11.
go back to reference Maurer MJ, Ghesquiéres H, Link BK et al (2018) Diagnosis-to-treatment interval is an important clinical factor in newly diagnosed diffuse large B-cell lymphoma and has implication for Bias in clinical trials. J Clin Oncol 36:1603–1610CrossRef Maurer MJ, Ghesquiéres H, Link BK et al (2018) Diagnosis-to-treatment interval is an important clinical factor in newly diagnosed diffuse large B-cell lymphoma and has implication for Bias in clinical trials. J Clin Oncol 36:1603–1610CrossRef
12.
go back to reference Kochenderfer JN, Sommerville RPT, Lu T et al (2017) Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol 35(16):1803–1813CrossRef Kochenderfer JN, Sommerville RPT, Lu T et al (2017) Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol 35(16):1803–1813CrossRef
13.
go back to reference Abramson J, Gordon L, Palomba ML et al (2018) Updated safety and long-term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagen maraleucel (JCAR017) in R/R aggressive NHL. J Clin Oncol 36(15suppl):7505CrossRef Abramson J, Gordon L, Palomba ML et al (2018) Updated safety and long-term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagen maraleucel (JCAR017) in R/R aggressive NHL. J Clin Oncol 36(15suppl):7505CrossRef
15.
go back to reference Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. In: International Agency for Research on Cancer (IARC), 4th edn. Lyon Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. In: International Agency for Research on Cancer (IARC), 4th edn. Lyon
16.
go back to reference Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282CrossRef Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282CrossRef
17.
go back to reference Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on no Hodgkin’s disease staging classification. Cancer Res 31:1860–1861PubMed Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on no Hodgkin’s disease staging classification. Cancer Res 31:1860–1861PubMed
18.
go back to reference Sykorova A, Belada D, Smolej L et al (2010) Staging of non-Hodgkin’s lymphoma –recommendations of the Czech Lymphoma Study Group. Klin Onkol 23:146–154PubMed Sykorova A, Belada D, Smolej L et al (2010) Staging of non-Hodgkin’s lymphoma –recommendations of the Czech Lymphoma Study Group. Klin Onkol 23:146–154PubMed
19.
go back to reference Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244CrossRef Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244CrossRef
20.
go back to reference Cheson BD, Pfistner B, Juweid ME et al (2007) International Harmonization Project on lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586CrossRef Cheson BD, Pfistner B, Juweid ME et al (2007) International Harmonization Project on lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586CrossRef
21.
go back to reference Shi Q, Schmitz N, Ou FS, Dixon JG, Cunningham D, Pfreundschuh M, Seymour JF, Jaeger U, Habermann TM, Haioun C, Tilly H, Ghesquieres H, Merli F, Ziepert M, Herbrecht R, Flament J, Fu T, Coiffier B, Flowers CR (2018) Progression-free survival as a surrogate end point for overall survival in first-line diffuse large B-cell lymphoma: an individual patient-level analysis of multiple randomized trials (SEAL). J Clin Oncol 36:2593–2602CrossRef Shi Q, Schmitz N, Ou FS, Dixon JG, Cunningham D, Pfreundschuh M, Seymour JF, Jaeger U, Habermann TM, Haioun C, Tilly H, Ghesquieres H, Merli F, Ziepert M, Herbrecht R, Flament J, Fu T, Coiffier B, Flowers CR (2018) Progression-free survival as a surrogate end point for overall survival in first-line diffuse large B-cell lymphoma: an individual patient-level analysis of multiple randomized trials (SEAL). J Clin Oncol 36:2593–2602CrossRef
22.
go back to reference Crump M, Neelapu SS, Farooq U, van den Neste E, Kuruvilla J, Westin J, Link BK, Hay A, Cerhan JR, Zhu L, Boussetta S, Feng L, Maurer MJ, Navale L, Wiezorek J, Go WY, Gisselbrecht C (2017) Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 130:1800–1808CrossRef Crump M, Neelapu SS, Farooq U, van den Neste E, Kuruvilla J, Westin J, Link BK, Hay A, Cerhan JR, Zhu L, Boussetta S, Feng L, Maurer MJ, Navale L, Wiezorek J, Go WY, Gisselbrecht C (2017) Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 130:1800–1808CrossRef
23.
go back to reference Blunt DN, Smyth L, Gatov E, Nagamuthu C, Buckstein R, Croxford R, Cheung M (2018) Diagnosis to treatment interval in DLBCL is predictive of overal survival in a large, population-based registry. Blood 132:1700CrossRef Blunt DN, Smyth L, Gatov E, Nagamuthu C, Buckstein R, Croxford R, Cheung M (2018) Diagnosis to treatment interval in DLBCL is predictive of overal survival in a large, population-based registry. Blood 132:1700CrossRef
24.
go back to reference Yelland LN, Kahan BC, Dent E, Lee KJ, Voysey M, Forbes AB, Cook JA (2018) Prevalence and reporting of recruitment, randomisation and treatment errors in clinical trials: a systematic review. Clin Trials 15(3):278–285CrossRef Yelland LN, Kahan BC, Dent E, Lee KJ, Voysey M, Forbes AB, Cook JA (2018) Prevalence and reporting of recruitment, randomisation and treatment errors in clinical trials: a systematic review. Clin Trials 15(3):278–285CrossRef
25.
go back to reference Fatola T, Rutherford SC, Allan JN, Ruan J, Furman RR, Zhengming C, Garcia A, Kong C, Bhavsar EB, Falsenfeld J, Leonard JP, Martin P (2018) Understanding the differences between clinical trial participants and real-world patients with non-Hodgkin lymphoma. Blood 132:2970CrossRef Fatola T, Rutherford SC, Allan JN, Ruan J, Furman RR, Zhengming C, Garcia A, Kong C, Bhavsar EB, Falsenfeld J, Leonard JP, Martin P (2018) Understanding the differences between clinical trial participants and real-world patients with non-Hodgkin lymphoma. Blood 132:2970CrossRef
26.
go back to reference Maurer MJ, Farooq U, Wahlen MM et al (2018) Short time between progression after immunochemotherapy and initiation of salvage therapy (PTI) is associated with inferior long-term outcomes in patients with relapsed/refractory DLBCL. ASH Annual Meeting; Abstract No 4204 Maurer MJ, Farooq U, Wahlen MM et al (2018) Short time between progression after immunochemotherapy and initiation of salvage therapy (PTI) is associated with inferior long-term outcomes in patients with relapsed/refractory DLBCL. ASH Annual Meeting; Abstract No 4204
27.
go back to reference Harrysson S, Eloranta S, Ekberg S, Enblad G, Jerkeman M, Hasselblom S, Wahlin BE, Andersson PO, Smedby KE (2018) Incidence and outcome of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a population-based cohort of 3165 patients in Sweden. Blood 132:2975CrossRef Harrysson S, Eloranta S, Ekberg S, Enblad G, Jerkeman M, Hasselblom S, Wahlin BE, Andersson PO, Smedby KE (2018) Incidence and outcome of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a population-based cohort of 3165 patients in Sweden. Blood 132:2975CrossRef
28.
go back to reference Galaznik A, Way N (2018) Patient characteristics and treatment paterns in the first-line and second-line treatment of diffuse large B-cell lymphoma and follicular lymphoma in the United Kingdom, France, and Germany. Blood 132:4232CrossRef Galaznik A, Way N (2018) Patient characteristics and treatment paterns in the first-line and second-line treatment of diffuse large B-cell lymphoma and follicular lymphoma in the United Kingdom, France, and Germany. Blood 132:4232CrossRef
29.
go back to reference Locke FL, Ghobaldi A, Jacobskon CA et al (2019) Long-term safety and activity of axicabtabene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol 20:31–42CrossRef Locke FL, Ghobaldi A, Jacobskon CA et al (2019) Long-term safety and activity of axicabtabene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol 20:31–42CrossRef
30.
go back to reference Neelapu SS, Locke FL, Bertlett et al (2017) Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531–2544CrossRef Neelapu SS, Locke FL, Bertlett et al (2017) Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377:2531–2544CrossRef
31.
go back to reference Schuster SJ, Bishop M, Tam C, Waller EK, Borchmann P, McGuirk J, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT, JULIET Investigators (2019) Tisagenlecleucel in adult relapsed and refractory diffuse large B-cell lymphoma. N Engl J Med 380:45–56CrossRef Schuster SJ, Bishop M, Tam C, Waller EK, Borchmann P, McGuirk J, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT, JULIET Investigators (2019) Tisagenlecleucel in adult relapsed and refractory diffuse large B-cell lymphoma. N Engl J Med 380:45–56CrossRef
32.
go back to reference Veldman-Jones MH, Lai Z, Wappett M, Harbron CG, Barrett JC, Harrington EA, Thress KS (2015) Reproducible, quantitative, and flexible molecular subtyping of clinical DLBCL samples using the nanostring Countersystem. Clin Cancer Res 21:2367–2378CrossRef Veldman-Jones MH, Lai Z, Wappett M, Harbron CG, Barrett JC, Harrington EA, Thress KS (2015) Reproducible, quantitative, and flexible molecular subtyping of clinical DLBCL samples using the nanostring Countersystem. Clin Cancer Res 21:2367–2378CrossRef
33.
go back to reference Greenawalt D, Liang WS, Saif S et al (2017) Comparative analysis of primary versus relapse/refractory DLBCL identifies shifts in mutation spectrum. Oncotarget 8:99237–99244CrossRef Greenawalt D, Liang WS, Saif S et al (2017) Comparative analysis of primary versus relapse/refractory DLBCL identifies shifts in mutation spectrum. Oncotarget 8:99237–99244CrossRef
Metadata
Title
The interval between progression and therapy initiation is the key prognostic parameter in relapsing diffuse large B cell lymphoma: analysis from the Czech Lymphoma Study Group database (NIHIL)
Authors
Andrea Janikova
Jozef Michalka
Zbynek Bortlicek
Renata Chloupkova
Vit Campr
Natasa Kopalova
Pavel Klener
Katerina Benesova
Jitka Hamouzova
David Belada
Vit Prochazka
Robert Pytlik
Jan Pirnos
Juraj Duras
Heidi Mocikova
Marek Trneny
Publication date
01-07-2020
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 7/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04099-y

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